Mitigating invalid data bias in the estimation of sexual orientation disparities in a survey of youth in US and Canada.

The current commentary explored the applicability of the methods described in "Mitigating invalid and mischievous survey responses: A registered report examining risk disparities between heterosexual and lesbian, gay, bisexual, or questioning youth" by Dr. Joseph Cimpian and colleagues to explore sexual orientation disparities in preexisting data from a nonprobability sample. Understanding Affirming Communities, Relationships, and Networks was a study of mostly White (77.4%) 9674 sexual and gender-minoritized youth aged 15-29 from the US and Canada. The influence of invalid data on the prevalence ratios of four health outcomes was assessed. The methods yielded similar effects to the original paper. The accuracy varied by outcome prevalence and was robust to misspecification of the model. Therefore, the applicability of this method to preexisting data seems feasible.

A mechanistic study of thiol addition to N-acryloylpiperidine.

Nucleophilic cysteine (Cys) residues are present in many enzyme active sites and represent the target of many different irreversible enzyme inhibitors. Given its fine balance between aqueous stability and thiolate reactivity, the acrylamide group is a particularly popular warhead pharmacophore among inhibitors designed for biological and therapeutic application. The acrylamide group is well known to undergo thiol addition, but the precise mechanism of this addition reaction has not been studied in as much detail. In this work we have focussed on the reaction of N-acryloylpiperidine (AcrPip), which represents a motif found in many targeted covalent inhibitor drugs. Using a precise HPLC-based assay, we measured the second order rate constants for the reaction of AcrPip with a panel of thiols possessing different pKa values. This allowed construction of a Brønsted-type plot that reveals the relative insensitivity of the reaction to the nucleophilicity of the thiolate. By studying temperature effects, we were able to construct an Eyring plot from which the enthalpy and entropy of activation were calculated. Ionic strength and solvent kinetic isotope effects were also studied, informing on charge dispersal and proton transfer in the transition state. DFT calculations were also performed, providing information on the potential structure of the activated complex. Taken together, these data strongly support one cohesive addition mechanism that is the microscopic reverse of the E1cb elimination, and highly relevant to the intrinsic thiol selectivity of AcrPip inhibitors and their subsequent design.

A kinetic study of thiol addition to N-phenylchloroacetamide.

Irreversible enzyme inhibitors bind covalently to their target and permanently limit its function. The redox-sensitive thiol group on the side chain of cysteine (Cys) residues is often the nucleophilic group that is targeted for reaction with the electrophilic warhead of irreversible inhibitors. While the acrylamide group is the warhead applied most frequently currently in the design of inhibitors with therapeutic potential, the chloroacetamide group offers a comparable reactivity profile. In that context, we have studied the details of the mechanism of thiol addition to N-phenylchloroacetamide (NPC). A kinetic assay was developed to accurately monitor the reaction progress between NPC and a small library of thiols with varying pKa values. From these data, a Brønsted-type plot was constructed, from which a ßnucRS- value of 0.22 ± 0.07 was derived, indicative of a relatively early transition state with respect to attack by the thiolate. The halide leaving group was also varied, for the reaction with one thiol, providing rate constants consistent with a transition state that is early with respect to leaving group departure. The effects of temperature and ionic strength were also studied, and all data are consistent with an early transition state for a concerted SN2 mechanism of addition. Molecular modelling was also performed, and these calculations confirm the concerted transition state and relative reactivity of the haloacetamides. Finally, this study allows a detailed comparison of the reactivity and reaction mechanisms of the chloroacetamide group with the benchmark acrylamides used in many irreversible inhibitor drugs.

Sampling Sexual and Gender Minority Youth With UnACoRN (Understanding Affirming Communities, Relationships, and Networks): Lessons From a Web-Based Survey.

BACKGROUND: Periodic surveys of sexual and gender minority (SGM) populations are essential for monitoring and investigating health inequities. Recent legislative efforts to ban so-called conversion therapy make it necessary to adapt youth surveys to reach a wider range of SGM populations, including those <18 years of age and those who may not adopt an explicit two-spirit, lesbian, gay, bisexual, transgender, and queer (2S/LGBTQ) identity. OBJECTIVE: We aimed to share our experiences in recruiting SGM youth through multiple in-person and online channels and to share lessons learned for future researchers. METHODS: The Understanding Affirming Communities, Relationships, and Networks (UnACoRN) web-based survey collected anonymous data in English and French from 9679 mostly SGM respondents in the United States and Canada. Respondents were recruited from March 2022 to August 2022 using word-of-mouth referrals, leaflet distribution, bus advertisements, and paid and unpaid campaigns on social media and a pornography website. We analyzed the metadata provided by these and other online resources we used for recruitment (eg, Bitly and Qualtrics) and describe the campaign's effectiveness by recruitment venue based on calculating the cost per completed survey and other secondary metrics. RESULTS: Most participants were recruited through Meta (13,741/16,533, 83.1%), mainly through Instagram; 88.96% (visitors: 14,888/18,179) of our sample reached the survey through paid advertisements. Overall, the cost per survey was lower for Meta than Pornhub or the bus advertisements. Similarly, the proportion of visitors who started the survey was higher for Meta (8492/18,179, 46.7%) than Pornhub (58/18,179, 1.02%). Our subsample of 7037 residents of Canada had a similar geographic distribution to the general population, with an average absolute difference in proportion by province or territory of 1.4% compared to the Canadian census. Our US subsample included 2521 participants from all US states and the District of Columbia. A total of CAD $8571.58 (the currency exchange rate was US $1=CAD $1.25) was spent across 4 paid recruitment channels (Facebook, Instagram, PornHub, and bus advertisements). The most cost-effective tool of recruitment was Instagram, with an average cost per completed survey of CAD $1.48. CONCLUSIONS: UnACoRN recruited nearly 10,000 SGM youth in the United States and Canada, and the cost per survey was CAD $1.48. Researchers using online recruitment strategies should be aware of the differences in campaign management each website or social media platform offers and be prepared to engage with their framing (content selection and delivery) to correct any imbalances derived from it. Those who focus on SGM populations should consider how 2S/LGBTQ-oriented campaigns might deter participation from cisgender or heterosexual people or SGM people not identifying as 2S/LGBTQ, if relevant to their research design. Finally, those with limited resources may select fewer venues with lower cost per completed survey or that appeal more to their specific audience, if needed.

A mechanistic study of thiol addition to N-phenylacrylamide.

Cysteine (Cys) residues contain a redox-sensitive thiol and are commonly found in enzyme active sites. In recent years, the presence of a reactive thiolate group on a protein has been exploited in the development of irreversible enzyme inhibitors as therapeutic agents. Many targeted covalent inhibitors (TCIs) are designed to covalently react with a specific Cys residue on a target protein active site, irreversibly modifying the target and inhibiting its normal function. The electrophilic warhead most commonly used in this way is the acrylamide functional group. Although the acrylamide group is well known for its ability to undergo thiol-addition reactions, very few studies have been conducted to elucidate the detailed mechanism of this reaction, which inspired us to conduct a thorough kinetic investigation. First, we developed a robust kinetic assay to accurately monitor reaction progress between N-phenylacrylamide (NPA) and a small library of alkyl thiols having widely varying pKa values. This allowed us to construct a Brønsted-type plot for the thiol addition reaction, revealing a ßnucRS- value of 0.07 ± 0.04. We also studied the solvent kinetic isotope effects (SKIEs), pH dependence, and temperature dependence of the reaction, which showed that reaction has a relatively large negative ΔS‡, and a small ΔH‡. Computational studies provided a structure for the transition state that is consistent with the experimental data. All of these data are consistent with rate-limiting nucleophilic attack, followed by rapid protonation of the enolate, corresponding to the microscopic reverse of the E1revcb elimination mechanism.

"Syndemic moral distress": sexual health provider practices in the context of co-occurring, socially produced sexual and mental health epidemics.

BACKGROUND: 'Syndemic' refers to socially produced, intertwined, and co-occurring epidemics. Syndemic theory is increasingly used to understand the population-level relationships between sexual health (including HIV) and mental health (including problematic substance use) epidemics. Syndemic-informed clinical interventions are rare. METHODS: We therefore asked 22 sexual health practitioners from six sexual health clinics in British Columbia, Canada to define the word 'syndemic' and then asked how the theory related to their clinical practice. RESULTS: Responses to syndemic theory ranged widely, with some practitioners providing nuanced and clinically informed definitions, others expressing a vague familiarity with the term, and others still having no prior knowledge of it. Where practitioners acknowledged the relevance of syndemic theory to their practice, they articulated specific ways in which syndemics create moral distress, that is, feeling that the most ethical course of action is different from what they are mandated to do. While some practitioners routinely used open-ended questions to understand the social and economic contexts of patients' sexual health needs, they described an uneasiness at potentially having surfaced concerns that could not be addressed in the sexual health clinic. Many observed persistent social, mental health, and substance use-related needs among their patients, but were unable to find feasible solutions to these issues. CONCLUSIONS: We therefore propose that interventions are needed to support sexual health practitioners in addressing psychosocial health needs that extend beyond their scope of practice, thereby reducing 'syndemic moral distress'.

Rumination, risk, and response: a qualitative analysis of sexual health anxiety among online sexual health chat service users.

BACKGROUND: Anxiety is common among sexual health service users. Accessible, anonymous online sexual health services may offer opportunities to connect users with mental health services, but little is known about anxiety in these settings. We sought to characterise expressions of anxiety among chat users and nurse responses to anxiety. METHODS: We conducted inductive thematic analysis of transcripts from an anonymous online sexual health chat service moderated by sexual health nurses. RESULTS: Among chat users, we identified: worry, anxiety, and emotional distress, particularly regarding HIV transmission risk, testing, and symptoms; exaggerated appraisal of HIV-transmission risk associated with sex-related shame and stigma; and patterns of anxiety that were unresolved by HIV education or testing interventions. Although nurses recognised and acknowledged anxiety, their responses to this anxiety varied; some provided anxiety management information, while others offered sexual health education and risk assessment. CONCLUSIONS: Targeted interventions addressing HIV-related stigma and anxiety among online sexual health service users are needed to facilitate connections to appropriate mental health supports.

Self-rated mental health among sexual health service clients during the first months of the COVID-19 pandemic, British Columbia, Canada.

We investigated self-reported mental health during the first three months of the COVID-19 pandemic (March-May 2020), using a survey of HIV-testing and sexual health service clients from British Columbia, Canada (N = 1198). Over half (55%) reported their mental health as poor at the beginning of the COVID-19 pandemic, more than double that of the general Canadian population in the same time frame (22%). Acknowledging that this burden of poor mental health that is likely to persist in the coming years, we propose that sexual health clinics should facilitate access to mental health supports as a low-barrier point of primary care contact.

The experience of medical communication in adults with acute leukemia: Impact of age and attachment security.

BACKGROUND: Health care providers' (HCPs) communication with cancer patients provides both information and support. Younger patient age and greater difficulty accepting support (attachment security) have been linked to poorer communication experiences with HCPs. The present secondary data analysis examined the impact of age group and attachment security on perceived communication problems with HCPs in adults with acute leukemia (AL). METHODS: The sample included 95 younger (age < 40 years) and 225 older (age ≥ 40 years) patients with newly diagnosed or recently relapsed AL. We assessed avoidant and anxious attachment security (reluctance to accept support and fear of its unavailability, respectively) with the modified 16-item Experiences in Close Relationships Scale. The impact of age group and attachment security on perceived communication problems, measured with the Cancer Rehabilitation Evaluation System-Medical Interaction Subscale, was assessed based on the presence and extent of communication problems. RESULTS: Younger patients (OR = 1.79-1.82, P = .030) and those with greater avoidant (OR = 1.44, P = .001) or anxious attachment (OR = 1.38, P = .009) were more likely to report communication problems. A similar relationship was found between age (ß's = -.17-.19, P = .015-.025), avoidant (ß = .29, P = .013), or anxious attachment (ß = .17, P = .031), and the extent of communication problems. A significant age-group × avoidant-attachment interaction (ß = -.31, P = .008) suggested that more avoidant attachment was associated with more perceived communication problems in the younger but not in the older group. CONCLUSIONS: Younger patients with AL, especially those more reluctant to seek or accept support, perceive more communication problems with their HCPs than older patients. Greater attention by HCPs to their communication with younger patients is needed.

Potent suppression of c-di-GMP synthesis via I-site allosteric inhibition of diguanylate cyclases with 2'-F-c-di-GMP.

Cyclic-di-GMP (c-di-GMP) is a central regulator of bacterial behavior. Various studies have implicated c-di-GMP in biofilm formation and virulence factor production in multitudes of bacteria. Hence it is expected that the disruption of c-di-GMP signaling could provide an effective means to disrupt biofilm and/or virulence factor formation in several bacteria of clinical relevance. C-di-GMP achieves the regulation of bacterial phenotype via binding to several effector molecules including transcription factors, enzymes and riboswitches. Crystal structure analyses of c-di-GMP effector molecules, in complex with the ligand, reveal that various classes of c-di-GMP receptors recognize this dinucleotide using different sets of recognition elements. Therefore, it is plausible that different analogues of c-di-GMP could be used to selectively modulate a specific class of c-di-GMP binding receptors, and hence modulate the bacterial phenotype. Thus far only a detailed study of the differential binding of c-di-GMP analogues to riboswitches, but not proteins, has been reported. In this report, we prepared various 2'-modified analogues of c-di-GMP and studied both polymorphisms of these analogues using DOSY NMR and the binding to several effector proteins, such as PilZ-containing proteins, diguanylate cyclases (DGC) containing I-sites, and phoshphodiesterases (PDE). 2'-Modification of c-di-GMP did not adversely affect the propensity to form higher aggregates, such as octameric forms, in the presence of potassium salts. Interestingly, we find that the selective binding to different classes of c-di-GMP binding proteins could be achieved with the 2'-modified analogues and that 2'-F analogue of c-di-GMP binds to the I-site of DGCs better (four times) than the native dinucleotide, c-di-GMP, whereas c-di-GMP binds to PDEs better (10 times) than 2'-F-c-di-GMP. 2'-F-c-di-GMP potently inhibits c-di-GMP synthesis by DGCs and hence raises the potential that cell permeable analogues of 2'-F-c-di-GMP could be used to disrupt c-di-GMP signaling in bacteria.

Geographic distribution of conversion therapy prevalence in Canada. Findings from a national cross-sectional survey, 2020.

BACKGROUND: Conversion therapy practices (CTPs) are discredited efforts that target lesbian, gay, bisexual, trans, queer, Two-Spirit, or other (LGBTQ2S+) people and seek to change, deny, or discourage their sexual orientation, gender identity, and/or gender expression. This study aims to investigate the prevalence of CTPs across Canadian provinces and territories and identify whether CTP bans reduce the prevalence of CTPs. METHODS: We collected 119 CTPs from 31 adults (18+) in Canada who have direct experience with CTPs, know people who have gone to CTPs, or know of conversion therapy practitioners using a 2020 anonymous online survey. Mapping analysis was conducted using ArcGIS Online. CTP prevalence was compared between provinces/territories with and without bans using chi-square tests. RESULTS: Three provinces and eleven municipalities had CTP bans. The prevalence of CTPs in provinces/territories with bans was 2.34 per 1,000,000 population (95% CI 1.65, 3.31). The prevalence of CTPs in provinces/territories without bans was 4.13 per 1,000,000 population (95% CI 3.32, 5.14). Accounting for the underlying population, provinces/territories with the highest prevalence of CTPs per 1,000,000 population were New Brunswick (6.69), Nova Scotia (6.50), and Saskatchewan (6.37). CONCLUSIONS: Findings suggest only 55% of Canadians were protected under CTP bans. The prevalence of CTPs in provinces/territories without bans was 1.76 times greater than provinces/territories with bans. CTPs are occurring in most provinces/territories, with higher prevalence in the west and the Atlantic. These findings and continued efforts to monitor CTP prevalence can help inform policymakers and legislators as society is increasingly acknowledging CTPs as a threat to the health and well-being of LGBTQ2S+ people.

The war on hTG2: warhead optimization in small molecule human tissue transglutaminase inhibitors.

Human tissue transglutaminase (hTG2) is a multifunctional enzyme with protein cross-linking and G-protein activity, both of which have been implicated in the progression of diseases such as fibrosis and cancer stem cell propagation when dysregulated, prompting the development of small molecule targeted covalent inhibitors (TCIs) possessing a crucial electrophilic 'warhead'. In recent years there have been significant advances in the library of warheads available for the design of TCIs; however, the exploration of warhead functionality in hTG2 inhibitors has remained relatively stagnant. Herein, we describe a structure-activity relationship study entailing rational design and synthesis for systematic variation of the warhead on a previously reported small molecule inhibitor scaffold, and rigorous kinetic evaluation of inhibitory efficiency, selectivity, and pharmacokinetic stability. This study reveals a strong influence on the kinetic parameters k inact and K I with even subtle variation in warhead structure, suggesting that the warhead plays a significant role in not only reactivity, but also binding affinity, which consequently extends to isozyme selectivity. Warhead structure also influences in vivo stability, which we model by measuring intrinsic reactivity with glutathione, as well as stability in hepatocytes and in whole blood, giving insight into degradation pathways and relative therapeutic potential of different functional groups. This work provides fundamental structural and reactivity information highlighting the importance of strategic warhead design for the development of potent hTG2 inhibitors.

Tautomerization and Isomerization in Quantitative NMR: A Case Study with 4-Deoxynivalenol (DON).

The regulated mycotoxin 4-deoxynivalenol (DON) has a heterocyclic structure that is readily amenable to tautomerization and conformational isomerization in solution. An analysis of DON in solution by NMR revealed the presence of hemiacetal tautomer(s) and putative conformational isomers, which maintain the intact enone functional group. The extent and type of tautomerization/isomerization vary according to the NMR solvent used and produce different signal patterns in the NMR spectra. Thus, the same proton produces multiple signals depending on which isomer/tautomer it belongs to. To maintain the accuracy of quantitative NMR (qNMR) measurements, it was essential to conclusively identify all signals belonging to the same proton to avoid underestimating its integral value. A strategy to overcome the complications of DON tautomerization and isomerization in solution during qNMR is reported. Of all proton atoms on the DON carbo-skeleton, H-10 produced clearly defined signals centered at 6.6 ppm for suspected conformational isomers and at 5.5 ppm for hemiacetal tautomers. To determine the purity of DON by quantitative proton NMR, the collective integrals of all isomeric and tautomeric signals belonging to H-10 provided the most accurate value. The purity of DON obtained with this protocol is highly accurate and suitable for the value assignment of certified reference materials (CRMs).

Violence, policing, and systemic racism as structural barriers to substance use treatment amongst women sex workers who use drugs: Findings of a community-based cohort in Vancouver, Canada (2010-2019).

BACKGROUND: Despite a high prevalence of substance use among women sex workers (SWs), rigorous social epidemiologic data on substance use treatment experiences among SWs remains limited. Given these gaps and the disproportionate burden of criminalization borne by Indigenous SWs, we evaluated (1) structural correlates of unsuccessful attempts to access substance use treatment; and (2) the interaction between policing and Indigenous ancestry on unsuccessful attempts to access treatment among SWs who use drugs. METHODS: Prospective data were from an open community-based cohort of women SWs (2010-2019) in Vancouver, Canada. Bivariate and multivariable logistic regression with generalized estimating equations(GEE) assessed correlates of unsuccessful attempts to access treatment. A multivariable GEE confounder model examined the interaction between Indigenous ancestry and policing on unsuccessful attempts to access treatment. RESULTS: Amongst 645 SWs who used drugs, 32.1 % reported unsuccessful attempts to access substance use treatment during the 9.5-year study. In multivariable GEE analysis, unsuccessful substance use treatment access was associated with identifying as a sexual/gender minority (AOR: 1.90, 95 %CI:1.37-2.63), opioid use (AOR: 1.43, 95 %CI: 1.07-1.91), and exposure to homelessness (AOR: 1.72; 95 %CI:1.33-2.21), police harassment (AOR: 1.48, 95 %CI:1.03-2.13), workplace violence (AOR: 1.80, 95 %CI: 1.31-2.49) and intimate partner violence (AOR: 2.11, 95 %CI:1.50-2.97). In interaction analysis, Indigenous SWs who experienced police harassment faced the highest odds of unsuccessful attempts to access substance use treatment (AOR: 2.59, 95 %CI:1.65-4.05). CONCLUSION: Findings suggest a need to scale-up culturally-safe, trauma-informed addictions, gender-based violence, and sex worker services, alongside dismantling of systemic racism across and beyond health and addictions services.

Determinants and Inequities in Sexual and Reproductive Health (SRH) Care Access Among Im/Migrant Women in Canada: Findings of a Comprehensive Review (2008-2018).

Given growing concerns of im/migrant women's access to sexual and reproductive health (SRH) services, we aimed to (1) describe inequities and determinants of their engagement with SRH services in Canada; and (2) understand their lived experiences of barriers and facilitators to healthcare. Using a comprehensive review methodology, we searched the quantitative and qualitative peer-reviewed literature of im/migrant women's access to SRH care in Canada from 2008 to 2018. Of 782 studies, 38 met inclusion criteria. Ontario (n = 18), British Columbia (n = 6), and Alberta (n = 6) were primary settings represented. Studies focused primarily on maternity care (n = 20) and sexual health screenings (n = 12). Determinants included health system navigation and service information; experiences with health personnel; culturally safe and language-specific care; social isolation and support; immigration-specific factors; discrimination and racialization; and gender and power relations. There is a need for research that compares experiences across diverse groups of racialized im/migrants and a broader range of SRH services to inform responsive, equity-focused programs and policies.

Structure-activity relationships of hydrophobic alkyl acrylamides as tissue transglutaminase inhibitors.

Tissue transglutaminase (TG2) is a multifunctional protein that plays biological roles based on its ability to catalyse protein cross-linking and to function as a non-canonical G-protein known as Ghα. The non-regulated activity of TG2 has been implicated in fibrosis, celiac disease and the survival of cancer stem cells, underpinning the therapeutic potential of cell permeable small molecule inhibitors of TG2. In the current study, we designed a small library of inhibitors to explore the importance of a terminal hydrophobic moiety, as well as the length of the tether to the irreversible acrylamide warhead. Subsequent kinetic evaluation using an in vitro activity assay provided values for the k inact and K I parameters for each of these irreversible inhibitors. The resulting structure-activity relationship (SAR) clearly indicated the affinity conferred by dansyl and adamantyl moieties, as well as the efficiency provided by the shortest warhead tether. We also provide the first direct evidence of the capability of these inhibitors to suppress the GTP binding ability of TG2, at least partially. However, it is intriguing to note that the SAR trends observed herein are opposite to those predicted by molecular modelling - namely that longer tether groups should improve binding affinity by allowing for deeper insertion of the hydrophobic moiety into a hydrophobic pocket on the enzyme. This discrepancy leads us to question whether the existing crystallographic structures of TG2 are appropriate for docking non-peptidic inhibitors. In the absence of a more relevant crystallographic structure, the data from rigorous kinetic studies, such as those provided herein, are critically important for the development of future small molecule TG2 inhibitors.

Challenges in the development of digital public health interventions and mapped solutions: Findings from a scoping review.

Background: "Digital public health" has emerged from an interest in integrating digital technologies into public health. However, significant challenges which limit the scale and extent of this digital integration in various public health domains have been described. We summarized the literature about these challenges and identified strategies to overcome them. Methods: We adopted Arksey and O'Malley's framework (2005) integrating adaptations by Levac et al. (2010). OVID Medline, Embase, Google Scholar, and 14 government and intergovernmental agency websites were searched using terms related to "digital" and "public health." We included conceptual and explicit descriptions of digital technologies in public health published in English between 2000 and June 2020. We excluded primary research articles about digital health interventions. Data were extracted using a codebook created using the European Public Health Association's conceptual framework for digital public health. Results and analysis: Overall, 163 publications were included from 6953 retrieved articles with the majority (64%, n = 105) published between 2015 and June 2020. Nontechnical challenges to digital integration in public health concerned ethics, policy and governance, health equity, resource gaps, and quality of evidence. Technical challenges included fragmented and unsustainable systems, lack of clear standards, unreliability of available data, infrastructure gaps, and workforce capacity gaps. Identified strategies included securing political commitment, intersectoral collaboration, economic investments, standardized ethical, legal, and regulatory frameworks, adaptive research and evaluation, health workforce capacity building, and transparent communication and public engagement. Conclusion: Developing and implementing digital public health interventions requires efforts that leverage identified strategies to overcome diverse challenges encountered in integrating digital technologies in public health.

Key recommendations for developing a national action plan to advance the sexual and reproductive health and rights of women living with HIV in Canada.

Action on the World Health Organization Consolidated guideline on sexual and reproductive health and rights of women living with HIV requires evidence-based, equity-oriented, and regionally specific strategies centred on priorities of women living with HIV. Through community-academic partnership, we identified recommendations for developing a national action plan focused on enabling environments that shape sexual and reproductive health and rights by, with, and for women living with HIV in Canada. Between 2017 and 2019, leading Canadian women's HIV community, research, and clinical organizations partnered with the World Health Organization to convene a webinar series to describe the World Health Organization Consolidated guideline, define sexual and reproductive health and rights priorities in Canada, disseminate Canadian research and best practices in sexual and reproductive health and rights, and demonstrate the importance of community-academic partnerships and meaningful engagement of women living with HIV. Four webinar topics were pursued: (1) Trauma and Violence-Aware Care/Practice; (2) Supporting Safer HIV Disclosure; (3) Reproductive Health, Rights, and Justice; and (4) Resilience, Self-efficacy, and Peer Support. Subsequent in-person (2018) and online (2018-2021) consultation with > 130 key stakeholders further clarified priorities. Consultations yielded five cross-cutting key recommendations:1. Meaningfully engage women living with HIV across research, policy, and practice aimed at advancing sexual and reproductive health and rights by, with, and for all women.2. Centre Indigenous women's priorities, voices, and perspectives.3. Use language that is actively de-stigmatizing, inclusive, and reflective of women's strengths and experiences.4. Strengthen Knowledge Translation efforts to support access to and uptake of contemporary sexual and reproductive health and rights information for all stakeholders.5. Catalyse reciprocal relationships between evidence and action such that action is guided by research evidence, and research is guided by what is needed for effective action.Topic-specific sexual and reproductive health and rights recommendations were also identified. Guided by community engagement, recommendations for a national action plan on sexual and reproductive health and rights encourage Canada to enact global leadership by creating enabling environments for the health and healthcare of women living with HIV. Implementation is being pursued through consultations with provincial and national government representatives and policy-makers.